|
| ||
|
|
||
Binding Effects (binding + effects)
Selected AbstractsTransungual iontophoretic transport of polar neutral and positively charged model permeants: Effects of electrophoresis and electroosmosisJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2008Jinsong Hao Abstract Transungual iontophoretic transport of model neutral permeants mannitol (MA), urea (UR), and positively charged permeant tetraethylammonium ion (TEA) across fully hydrated human nail plates at pH 7.4 were investigated in vitro. Four protocols were involved in the transport experiments with each protocol divided into stages including passive and iontophoresis transport of 0.1 and 0.3 mA. Water and permeant uptake experiments of nail clippings were also conducted to characterize the hydration and binding effects of the permeants to the nails. Iontophoresis enhanced the transport of MA and UR from anode to cathode, but this effect (electroosmosis) was marginal. The transport of TEA was significantly enhanced by anodal iontophoresis and the experimental enhancement factors were consistent with the Nernst,Planck theory predictions. Hindered transport was also observed and believed to be critical in transungual delivery. The barrier of the nail plates was stable over the time course of the study, and no significant electric field-induced alteration of the barrier was observed. The present results with hydrated nail plates are consistent with electrophoresis-dominant (the direct field effect) transungual iontophoretic transport of small ionic permeants with small contribution from electroosmosis. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:893,905, 2008 [source] Relevant activities of extracts and constituents of animals used in traditional Chinese medicine for central nervous system effects associated with Alzheimer's diseaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2006Yuhao Ren The centipede Scolopendra subspinipes mutilans L. Koch (,Wugong'), the beetle Mylabris phalerata Pallas (,Ban mao') and the earthworm Pheretima aspergillum Chen (,DiLong') have a reputation in traditional Chinese medicine for reducing symptoms of central nervous system decline, including memory loss. A series of extracts of all three organisms was tested for acetylcholinesterase (AChE) inhibition and copper ion binding effects, the latter likely to reduce oxidative damage caused by excess copper. The beetle and centipede chloroform extracts showed the strongest AChE inhibitory effects (30.6% inhibition at 105 ,g mL,1 and 32.3% inhibition at 167 ,g mL,1, respectively) and, in the case of the centipede, this was traced to the unsaturated fatty acids present using bioassay-guided fractionation. Cantharidin from the beetle was shown to have AChE activity (31% inhibition at 1 ,M, 0.196,g mL,1), making it a major contributor to the activity of the beetle extract. The earthworm showed no AChE inhibitory activity. Since unsaturated fatty acids have not been previously reported to have AChE inhibitory activity, a series of related compounds was tested to determine structure-activity relationships. It was found that activity existed where there was a chain length of more than 16 C atoms with at least one unsaturated bond in the chain. The carboxylic acid group was also necessary for activity. The fatty acids present in the centipede also showed the ability to bind copper ions when tested using a novel thin layer chromatography method designed to detect copper-binding compounds. The activities reported give some support to the use of the beetle and centipede in traditional Chinese medicine for improving cognitive function. [source] Quantum dot-based protein micro- and nanoarrays for detection of prostate cancer biomarkersPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 9 2008Anisha Gokarna Abstract In this article, we demonstrate the fabrication and detection of cancer protein biochips consisting of micro- and nanoarrays whereby pegylated quantum dots (QDs) conjugated to antibodies (Abs) of prostate specific antigens (PSA) were used for the detection of clinical biomarkers such as PSA. BSA which acts as an efficient blocking layer in microarrays, tends to show an interaction with QDs. In view of this fact, we investigated two series of samples which were fabricated in the presence and absence of BSA blocking layer. Variation in the incubation time required for the antigen,antibody interaction to take place, different proteins as controls and the effect of bare QDs on these microarrays, were the three main parameters which were studied in these two series. Samples fabricated in the absence of BSA blocking layer exhibited an extremely high specificity in the detection of cancer proteins and were also marked by negligible nonspecific binding effects of QDs, in stark contrast to the samples fabricated using BSA as a blocking layer. Fabrication of nanoarrays of QD-conjugated PSA Abs having a spot size of nearly 900,nm has also been demonstrated. Thus, we show the potential offered by QDs in in vitro analysis of cancer biomarker imaging. [source] Carbohydrate-binding properties of goat secretory glycoprotein (SPG-40) and its functional implications: structures of the native glycoprotein and its four complexes with chitin-like oligosaccharidesACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2007Punit Kaur A 40,kDa glycoprotein (SPG-40) secreted during involution works as a protective signalling factor through its binding to viable cells. The crystal structure of the native protein has been determined at 2.3,Å resolution. This is the first report on the carbohydrate-binding properties of SPG-40; the structure determinations of the complexes of SPG-40 with four oligosaccharides of different lengths at resolutions ranging from 2.2 to 2.8,Å are described. Carbohydrate-binding studies with N -acetylglucosamines (GlcNAcn, n = 3,6) using fluorescence spectroscopy revealed poor binding effects with GlcNAc3 and GlcNAc4, while GlcNAc5 and GlcNAc6 bound to SPG-40 with considerable strength; the dissociation constants (Kd) were estimated to be 260 ± 3 and 18 ± 4,µM, respectively. SPG-40 was cocrystallized with GlcNAc3, GlcNAc4, GlcNAc5 and GlcNAc6. The overall structure of native SPG-40 was essentially similar to that reported previously at low resolution. The structures of its complexes with GlcNAc3, GlcNAc4, GlcNAc5 and GlcNAc6 revealed the positions of these oligosaccharides in the carbohydrate-binding groove and provided insights into the mechanism of binding of oligosaccharides to SPG-40, indicating that the preferred subsites in the carbohydrate-binding groove of SPG-40 were from ,4 to ,2. The structure of the protein remained unperturbed upon binding of GlcNAc3 and GlcNAc4, but the structure changed significantly upon binding of GlcNAc5 and GlcNAc6. Significant conformational variations were observed in the sugar-binding groove: Trp78 partially flipped out of the barrel in GlcNAc5, while in the GlcNAc6 complex a completely flipped-out Trp78 was observed along with several other conformational changes, including those of Asp186 and Arg242. Such changes upon binding to carbohydrates have not previously been observed in chitin-hydrolyzing chitinases and reflect less favourable binding of carbohydrates to SPG-40. As this appears to essentially be a binding protein, this loss of binding affinity might be compensated by other intermolecular interactions such as protein,protein interactions and also by the binding of its own glycan chain. [source] The ,apparent clearance' of free phenytoin in elderly vs. younger adultsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2010Daniel F. B. Wright WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The clearance of many drugs is reduced in the elderly, but the data regarding phenytoin are conflicting. Most studies have estimated phenytoin metabolic clearance using total drug concentrations (bound plus unbound), which may be confounded by protein binding effects. Free phenytoin concentrations are independent of protein binding and should more accurately reflect true metabolic clearance changes in elderly patients. WHAT THIS STUDY ADDS , The two studies reported in this paper suggest a trend towards reduced free phenytoin ,apparent clearance' in the elderly, although statistically significant results were not found. Other published studies have largely found similar trends, suggesting an age effect. AIMS To test the hypothesis that the ,apparent clearance' of free phenytoin is reduced in elderly patients. METHODS Two separate studies were conducted comparing free phenytoin ,apparent clearance' in elderly vs. younger adults. The first study was a retrospective analysis of free phenytoin concentrations measured at Christchurch Hospital from 1997 to 2006. In the second study free phenytoin concentrations were measured prospectively in ambulatory subjects who were taking phenytoin regularly. RESULTS In the retrospective study (n= 29), free phenytoin ,apparent clearance' was 0.27 ± 0.04 l kg,1 day,1 (95% CI 0.19, 0.34) in the elderly cohort vs. 0.37 ± 0.06 l kg,1 day,1 (95% CI 0.22, 0.52) in younger adults, but the difference was not statistically significant. In the prospective study, free phenytoin ,apparent clearance' showed a non-significant trend to being reduced in the elderly patients (0.12 ± 0.02 l kg,1 day,1, 95% CI 0.07, 0.17) compared with the younger cohort (0.18 ± 0.07 l kg,1 day,1, 95% CI 0.09, 0.26) in those not taking interacting drugs (n= 21). CONCLUSIONS This research does not prove the hypothesis that the ,apparent clearance' of free phenytoin is reduced in the elderly. However, the trends found in these two studies are supported by trends in the same direction in other published studies, suggesting an age effect. [source] | |||||||||||||